PET Imaging Serotonin Biomarker May Predict Suicide Risk

There is a clear need for methods to help identify individuals at risk of suicide, and certain biomarkers could aid in such efforts.
There is a clear need for methods to help identify individuals at risk of suicide, and certain biomarkers could aid in such efforts.

According to statistics from the Centers for Disease Control, a suicide occurs every 13 minutes in the US.1 While there were more than
41 000 known suicides in 2013, an additional 1.3 million adults had attempted suicide in the previous year, and 2.7 million people made a plan to do so. There is a clear need for methods to help identify individuals at risk of suicide, and certain biomarkers could aid in such efforts. Using positron emission tomography (PET) imaging, a study published in JAMA Psychiatry explored whether serotonin binding potential predicts future suicide attempts and ideation, as well as intent and lethality of suicidal behavior.2

Previous cross-sectional findings showed reduced serotonin transporter binding potential in the midbrain of people with depression who had attempted suicide, as well as increased serotonin1A binding potential in the raphe nuclei (RN) of those whose attempts involved more lethal methods and greater suicidal intent and ideation. In the current study, researchers at Columbia University and Stony Brook University School of Medicine in New York conducted the first prospective, observational investigation extending these lines of inquiry.

One hundred adult patients receiving treatment in the community for major depressive disorder (MDD) were followed for a period of 2 years. In addition to a routine history, physical examination, blood tests, and urine toxicology screening at baseline, patients underwent PET scans and were assessed using the Structured Clinical Interview for DSM-IV, the Hamilton Depression Rating Scale, the Beck Depression Inventory, the Beck Scale for Suicide Ideation (BSSI), and several other tools. Suicidal ideation was assessed at 3, 12, and 24 months, and each patient who attempted suicide during the study period was again assessed for suicidal intent and lethality.

The findings show that 15 of the 100 patients attempted suicide during the study period, 2 of whom were completers. The imaging results were as follows:

  • Higher serotonin1A binding potential in the RN predicted more suicidal ideation at 3 and 12 months [(b = 0.02; t = 3.45; P =.001) and (b = 0.02; t = 3.63; P =.001), respectively], and greater lethality of suicidal behavior (b = 0.08; t = 2.89; P =.01).
  • Higher serotonin1A binding potential of the insula (t = 2.41; P =.04), anterior cingulate (t = 2.27; P =.04), and dorsolateral prefrontal cortex (t = 2.44; P =.03) also predicted lethality of suicidal behavior.
  • Contrary to the authors' hypotheses, serotonin1A binding potential did not predict suicidal intent (F1,10 = 0.83; P =.38), and midbrain serotonin transporter binding potential did not predict future attempts (log-rank χ21 = 0.4; P = .54), though this could have been due to insufficient statistical power.

Though further research is needed to identify precise mechanisms, the effects observed in the present study could be mediated by serotonergic dysfunction, which may lead to impairments in mood, decision-making, and social and emotional cognition.

“Identifying neurobiological characteristics of high-lethality suicide attempters has intrinsic scientific importance, and discovery of molecular-level markers of high-lethality behavior may eventually improve clinical screening to detect those at risk for suicide,” the authors noted.

References

  1. Centers for Disease Control and Prevention. Suicide–facts at a glance. Retrieved on 11/3/16 from https://www.cdc.gov/violenceprevention/pdf/suicide-datasheet-a.pdf
  2. Oquendo MAGalfalvy H, Sullivan GM, et al. Positron emission tomographic imaging of the serotonergic system and prediction of risk and lethality of future suicidal behavior. JAMA Psychiatry. 2016; 73(10):1048-1055.
  3.  Miller JM, Hesselgrave N,Ogden RT, et al. Positron emission tomography quantification of serotonin transporter in suicide attempters with major depressive disorder. Biol Psychiatry. 2013; 74(4):287-95.
  4. Nye JAPurselle DPlisson C, et al. Decreased brainstem and putamen SERT binding potential in depressed suicide attempters using [11C]-zient PET imaging. Depress Anxiety. 2013; 30(10):902-7.
  5. Sullivan GMOquendo MAMilak M, et al. Positron emission tomography quantification of serotonin(1A) receptor binding in suicide attempters with major depressive disorder. JAMA Psychiatry. 2015; 72(2):169-78.
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